Drug-induced liver injury: What would a liver doctor do?

Drug-induced liver injury is a significant cause of morbidity. Practical management strategies for suspected drug-induced liver injury, including useful investigations and appropriate referral, are proposed in this case-based article

Mechanisms and Implications of Age-Related Changes in the Liver: Nonalcoholic Fatty Liver Disease in the Elderly

Nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis associated with metabolic abnormalities such as overweight/central obesity, insulin resistance, type 2 diabetes (T2D), and dyslipidemia. NAFLD is becoming the most common liver disease in contemporary society, with the highest prevalence in those over 60 years. NAFLD pathology ranges from simple steatosis to a necroinflammatory fibrosing disorder called steatohepatitis (SH), the latter associated with high risk of developing cirrhosis, often occuring in the seventh to ninth decades of life. While the main health implications of NAFLD are increased risk of developing T2D, cardiovascular diseases, and common cancers, there is substantantially increased standardized mortality, and deaths from decompensated cirrhosis and hepatocellular carcinoma (HCC). Little is known about the interactive effects of ageing and NAFLD, with most studies focusing on the younger population. This paper summarises the epidemiology, pathogenesis, and clinical course of NAFLD, with particular attention to persons over age 60 years. An approach to the management of NASH and its complications in the elderly, will also be presented here

The relationship between transformational leadership and customer-orientated boundary-spanning behaviours:examining the role of compassion

Customer-oriented boundary-spanning behaviours (COBSBs) are critical to the success of service organisations. Transformational leadership, with its emphasis on the social elements of the leader-subordinate dyad, is a likely antecedent to COBSBs. Similarly, the interpersonal nature of services suggests leader compassion could have a significant effect on the saliency of the relationship between transformational leadership and COBSBs. This paper reports on a study of the moderating effect of leader compassion on the relationship between transformational leadership and COBSBs (service delivery behaviours, internal influence and external representation). Transformational leadership and compassion both have significant and positive influences on COBSBs. However, compassion plays no moderating role. These findings are discussed and avenues for further research are proposed

A model of service performance enhancement:the role of transactional and transformational leadership

This paper is concerned with the ways in which transactional and transformational leadership styles can improve the service performance of front-line staff. Past literature on services marketing has indicated the importance of leadership but has largely ignored the parallel literature in which leadership styles have been conceptualized and operationalized (e.g., sales management, organizational psychology). This paper seeks to build upon existing services marketing theory by introducing the role of leadership styles in enhancing service performance. Consequently, a conceptual framework of the effect of transactional and transformational leadership styles on service performance, anchored in a crossdisciplinary literature review, is developed. Managerial implications and future research directions are also discussed

A model of transactional and transformational leadership for services personnel

This paper is concerned with the effects that leadership styles (i.e., transactional and transformational) can have upon the level of front-line employees’ service delivery quality. Previous literature has mostly looked at leadership and its effects upon subordinates within a sales, psychology, or human resources context. However, due to the idiosyncrasies inherent in services (i.e., intangibility, heterogeneity, perishability, and inseparability), it is likely that, in such a context, different leadership styles will effect performance outcomes. Consequently, this paper seeks to expand the services marketing literature by developing a conceptual framework of leadership style effects adapted to the field of services marketing. Of particular importance are the effects that leadership styles have upon front-line employee “motivators” and service-related job outcomes. Specific hypotheses are developed and future research directions are also presented for consideration

NASH is an inflammatory disorder: Pathogenic, prognostic and therapeutic implications

While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed infl ammatory cell infi ltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about infl ammatory recruitment, despite its importance for the perpetuation of liver injury and fi brogenesis. In this review, we present evidence that liver infl ammation has prognostic signifi cance in NAFLD. We then consider the origins and components of liver infl ammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly infl ammasome. The key pro-infl ammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that infl ammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, infl amed adipose tissue and circulating infl ammatory cells. We briefl y review these mechanistic considerations and project their implications for the effective treatment of NASH

Service encounter conceptualisation:employees' service behaviours and customers' service quality perceptions

The enhancement of service quality is an area of optimal managerial relevance that has, to date, received minimal attention in the literature. Because customers' service quality evaluations are based almost entirely upon the behaviours of frontline employees, organisations rely heavily upon these employees to improve overall service quality provision. However, much of the literature looking at service quality enhancement lacks detail when examining the impact of employee service-related behaviours on customers' service quality perceptions. As a result, this paper comprehensively conceptualises those front-line employee behaviours which are the most likely to enhance customers' service quality perceptions. This conceptualisation is grounded in an extensive review of the services marketing literature, pooling together previously disparate research strands. Formal hypotheses are presented. Implications and future research directions are also discussed

Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH

Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant ( foz/foz ) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a ) vehicle control, b ) ezetimibe (5 mg/kg/day), c ) atorvastatin (20 mg/kg/day), or d ) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα -positive (activated) KCs forming CLSs ( ≥ 3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation